This study offers a comprehensive examination of the clonal dynamics of invasive pneumococcal isolates in Denmark from the summer of 2019 to the end of 2023. We utilized GPSCs, STs, and serotype distribution data to analyze the impact of vaccination strategies and public health interventions on pneumococcal population structures and pathogen evolution. The implementation of tools such as the Global Pneumococcal Sequencing project and PubMLST facilitated accurate assignment of GPSCs, enhancing our understanding of global pneumococcal population structure^21,22.

Our investigation identified three key GPSCs in Denmark: GPSC3 (serotypes 8 and 33F), GPSC12 (serotype 3), and GPSC19 (serotype 22F) during the study period (2019–2023) (Fig. 1). These GPSCs have also been observed in other countries, albeit with variations in dominance. In a Canadian study (2011–2020) they identified GPSC3 (serotypes 8/33F), GPSC19 (22F), GPSC5 (23A), GPSC26 (12F), GPSC12 (serotype 3), and GPSC27 (serotype 4) as the most prevalent lineages⁹. In Central and Northwestern Russia (2011–2018), GPSC1 (CC320) expressing serotypes 19A/19F, GPSC3 (CC53/62/1012) expressing serotypes 8/11A, GPSC7 (CC439) expressing serotypes 23A/23F, GPSC47 (CC386) expressing serotypes 6B/6C, and GPSC12 (CC180) expressing serotype 3 were predominant²³. Similarly, in Southern India (1991–2020), dominant GPSCs included 1, 2, 6, 8, 9, 10, and 23²⁴. An international study on pneumococcal lineages post-PCV-13 found GPSCs 3, 19, 11, 5, 38, 26, 36, 48, 9, and 7 as dominant, with other important lineages being GPSCs 59, 55, 168, 25, 6, 139, and 132²².

The variations in dominant GPSCs across countries likely stem from differences in childhood vaccination programs, vaccination strategies for the elderly, and pandemic restrictions. For example, the introduction of PCV-13 in the Danish childhood vaccination program significantly altered the GPSC lineage for serotype 24F, transitioning from ST72 (GPSC16) to ST162 (GPSC6)¹⁰. The ST162/serotype 24F lineage has been described as more successful than ST72/serotype 24F²⁵. A Danish study on serotype 8 showed that PCV introduction did not affect the clonal prevalence, with GPSC3 (ST53/serotype 8) remaining dominant from the 1960s through the PCV-7 and PCV-13 eras¹². However, recent declines in GPSC3 (ST53/serotype 8) has been linked to PPV-23 vaccination in the elderly and COVID-19 pandemic restrictions⁴. These findings align with other studies showing the evolving pneumococcal landscape under vaccine pressure.

The implementation of COVID-19 preventive measures in March 2020 and the subsequent introduction of the 23-valent pneumococcal polysaccharide vaccine (PPV23) into the senior vaccination program had significant impacts on IPD dynamics in Denmark^4,5. The study period revealed a marked reduction in the number of invasive isolates, particularly during 2020 and 2021, corresponding to the stringent COVID-19 restrictions²⁶. The PPV23 vaccination program further contributed to this decline, especially protecting individuals aged 65 and older against various IPD serotypes, including serotypes 8 and 22F^4,5. However, the persistence of serotype 3 IPD cases underscores the ongoing challenge in achieving comprehensive vaccine coverage for all serotypes.

Surprisingly, although COVID-19 restrictions and PPV23 vaccination did reduce the number of IPD cases and changed the serotype and MLST distribution, the GPSC lineages were found to be stable, with no major changes (Fig. 1A, Figs. 4, 5, and 6).

While GPSCs provide a standardized and globally recognized framework for comparing pneumococcal lineages^8,9, they may not always reflect finer-scale epidemiological changes. In our study, significant fluctuations in serotype prevalence were not always mirrored at the GPSC level, suggesting that GPSCs may mask important serotype–ST shifts relevant to vaccine surveillance. In the Danish context, where routine serotyping and MLST are established, analyses at the serotype and sequence type level may offer greater resolution for tracking emerging trends, detecting potential outbreaks, and evaluating the impact of vaccination programmes^3,27. This distinction is important when selecting analytical frameworks for national-level public health surveillance.

This study offers a comprehensive analysis of pneumococcal population dynamics in Denmark; however, several limitations should be acknowledged. The analysis focused on trends in GPSCs in relation to overall serotype distribution and did not stratify isolates by focus of infection or age group. Although cerebrospinal fluid isolates are included, the limited number of cases prevented more detailed demographic or clinical subgroup analyses.

The study period began in August 2019 with the initiation of routine WGS in Denmark. As a result, it was not possible to evaluate GPSC or sequence type dynamics prior to this date. Additionally, AMR patterns were not assessed, despite the known association between GPSCs and AMR profiles. The scope of this study was deliberately limited to serotype and sequence type dynamics in the context of vaccine impact and national surveillance.